We have studied in recent years the properties and mechanism of action at cellular level of a series of structurally related peptides extracted from the intestine, particularly VIP (Vasoactive Intestinal Peptide) and secretin. We have shown that VIP stimulates intestinal secretion strongly and biliary and pancreatic secretion weakly. VIP, like secretin inhibits gastric secretion. Like glucagon, VIP is glycogenolytic and capable independently of the increase in blood glucose of stimulating both glucagon and insulin release. In more recent studies, we have defined the mechanisms of action of VIP and secretin on colonic secretion and shown these to be nucleotide-dependent. The lactamimide RMI 12330A and somatostatin inhibit VIP-stimulated secretion and may be of therapeutic value. Earlier we had studied the properties of VIP and secretin on smooth muscle from the intestine and gallbladder in vitro. Recently, we have developed a technique in mammals which enables us to study isolated smooth muscle cells by morphometric techniques. The cells are obtained in the relaxed state and respond well to hormones. We have also studied the structure-activity relations of VIP and secretin on pancreatic secretion in the rat. Synthetic fragments ranging from secreting 5-27 to secretin 22-27 are active: their activity is mostly manifested after secretin itself had first been given. We postulate that the fragments owe their activity largely to their competition with discharge of tightly bound secretin on pancreatic cells. It seems likely also that the effect of VIP is at least in part due to the same phenomenon. BIBLIOGRAPHIC REFERENCES: Bitar, K.N., Zfass A.M. and Makhlouf, G.M. Activity of C-terminal partial sequences of secretin. Cl. Res. 25: in press, 1977. Bitar, K.N., Zfass A.M., Farrar J.T. and G.M. Makhlouf. Isolated gastric muscle cells: Demonstration of the direct myogenic effect of cholecystokinin. Gastroenterology 72: N degrees 5, in press, 1977.